Location: Phillips 2008 @ 33593e5118d1 / phillips_baseline_2008.cellml

Author:
Hanne <Hanne@hanne-nielsens-macbook.local>
Date:
2010-07-08 11:27:10+12:00
Desc:
Added xul and clickabel sessions for both models
Permanent Source URI:
https://staging.physiomeproject.org/workspace/phillips_2008/rawfile/33593e5118d100c860fa6125b06842747e597d7e/phillips_baseline_2008.cellml

<?xml version="1.0"?>
<model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xml:base="file:///home/jlaw060/cellml_repository/pmr2/phillips_2008/phillips_baseline_2008.cellml" cmeta:id="phillips_2008" name="phillips_2008">
	
	<documentation xmlns="http://cellml.org/tmp-documentation">
		<article>
			<articleinfo>
				<title>Sleep deprivation in a quantitative physiologically based model of the ascending arousal system</title>
				<author>
					<firstname>Catherine</firstname>
					<surname>Lloyd</surname>
					<affiliation>
						<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
					</affiliation>
				</author>
			</articleinfo>
			<sect1 id="sec_status">
				<title>Model Status</title>
				<para>
    This CellML model replicates the "baseline" version of the original Phillips and Robinson 2008 model.  It runs in both PCEnv and COR to replicate figure 2 in the paper (using the old nominal values from table one).  The units have been checked and they are consistent.  Note that the model has to be run for at least 3 cycles for it to stabilse into steady oscillations.
</para>
        </sect1>
        <sect1 id="sec_structure">
				<title>Model Structure</title>
				<para>
Abstract: A physiologically based quantitative model of the human ascending arousal system is used to study sleep deprivation after being calibrated on a small set of experimentally based criteria. The model includes the sleep-wake switch of mutual inhibition between nuclei which use monoaminergic neuromodulators, and the ventrolateral preoptic area. The system is driven by the circadian rhythm and sleep homeostasis. We use a small number of experimentally derived criteria to calibrate the model for sleep deprivation, then investigate model predictions for other experiments, demonstrating the scope of application. Calibration gives an improved parameter set, in which the form of the homeostatic drive is better constrained, and its weighting relative to the circadian drive is increased. Within the newly constrained parameter ranges, the model predicts repayment of sleep debt consistent with experiment in both quantity and distribution, asymptoting to a maximum repayment for very long deprivations. Recovery is found to depend on circadian phase, and the model predicts that it is most efficient to recover during normal sleeping phases of the circadian cycle, in terms of the amount of recovery sleep required. The form of the homeostatic drive suggests that periods of wake during recovery from sleep deprivation are phases of relative recovery, in the sense that the homeostatic drive continues to converge toward baseline levels. This undermines the concept of sleep debt, and is in agreement with experimentally restricted recovery protocols. Finally, we compare our model to the two-process model, and demonstrate the power of physiologically based modeling by correctly predicting sleep latency times following deprivation from experimental data.
				</para>
				
				<para>
The original paper reference is cited below:
				</para>
				
				<para>
					Sleep deprivation in a quantitative physiologically based model of the ascending arousal system, A.J.K. Phillips and P.A. Robinson, 2008,  
						<emphasis>Journal of Theoretical Biology</emphasis>, 255, 413-423.  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=18805427&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 18805427</ulink>
				</para>
				
				<informalfigure float="0" id="fig_reaction_diagram">
					<mediaobject>
						<imageobject>
							<objectinfo>
								<title>model diagram</title>
							</objectinfo>
							<imagedata fileref="phillips_2008.png"/>
						</imageobject>
					</mediaobject>
					<caption>Schematic diagram of the Phillips and Robinson 2008 sleep model. MA is the monoaminergic group, ACh is acetylcholine, VLPO represents the ventrolateral preoptic area, and D is the drive input which consists of circadian and homeostatic components.</caption>
				</informalfigure>
			</sect1>
		</article>
	</documentation>
 
 
 <units name="mV">
    <unit prefix="milli" units="volt"/>
 </units>
 
 <units name="mV_second">
    <unit units="mV"/>
    <unit units="second"/>
 </units>
 
 <units name="mV_per_second">
    <unit units="mV"/>
    <unit exponent="-1" units="second"/>
 </units>
 
 <units name="mV_per_nM">
    <unit units="mV"/>
    <unit exponent="-1" units="nM"/>
 </units>
 
 <units name="per_second">
    <unit exponent="-1" units="second"/>
 </units>
 
 <units name="hour">
    <unit multiplier="3600" units="second"/>
 </units>
 
 <units name="per_hour">
    <unit exponent="-1" units="hour"/>
 </units>
 
 <units name="second_per_hour">
    <unit units="second"/>
    <unit exponent="-1" units="hour"/>
 </units>
 
 <units name="nM">
    <unit prefix="nano" units="mole"/>
    <unit exponent="-1" units="litre"/>
 </units>
 
 <units name="nM_second">
    <unit units="nM"/>
    <unit units="second"/>
 </units>
 

 <component name="environment">
    <variable cmeta:id="environment_time" name="time" public_interface="out" units="hour"/>
 </component>

 <component name="v">
    <variable name="Qv" public_interface="out" units="per_second"/>
    <variable cmeta:id="v_Vv" initial_value="-6.0" name="Vv" public_interface="out" units="mV"/>
	
	<variable initial_value="10.0" name="tau_v" units="second"/>
	<variable initial_value="-1.9" name="v_vm" units="mV_second"/>
    
	<variable name="Qm" public_interface="in" units="per_second"/>
	<variable name="Qmax" public_interface="in" units="per_second"/>
	<variable name="D" public_interface="in" units="mV"/>
    <variable name="theta" public_interface="in" units="mV"/>
    <variable name="sigma" public_interface="in" units="mV"/>
    <variable name="time" public_interface="in" units="hour"/>
    
	<math xmlns="http://www.w3.org/1998/Math/MathML" id="1">
       <apply>
          <eq/>
          <ci>Qv</ci>
          <apply>
             <divide/>
             <ci>Qmax</ci>
             <apply>
                <plus/>
				<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                <apply>
                   <exp/>
				   <apply>
                      <divide/>
					  <apply>
                         <minus/>
						 <apply>
                            <minus/>
                            <ci>Vv</ci>
							<ci>theta</ci>
                         </apply>
					  </apply>
					  <ci>sigma</ci>
				   </apply>
                </apply>
             </apply>
          </apply>
       </apply>
	</math>
	
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="2">	
	   <apply>
          <eq/>
          <apply>
             <diff/>
             <bvar>
                <ci>time</ci>
             </bvar>
             <ci>Vv</ci>
          </apply>
          <apply>
             <divide/>
			 <apply>
                <minus/>
				<apply>
                   <plus/>
				   <apply>
                      <times/>
					  <ci>v_vm</ci>
					  <ci>Qm</ci>
                   </apply>
				   <ci>D</ci>
                </apply>
				<ci>Vv</ci>
             </apply>
			 <apply>
                <divide/>
				<ci>tau_v</ci>
				<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second_per_hour">3600</cn>
			 </apply>
          </apply>
	   </apply>
	</math>
 </component>
 
 <component name="m">
    <variable name="Qm" public_interface="out" units="per_second"/>
    <variable cmeta:id="m_Vm" initial_value="0.0" name="Vm" public_interface="out" units="mV"/>
	
	<variable initial_value="10.0" name="tau_m" units="second"/>
	<variable initial_value="-1.9" name="v_mv" units="mV_second"/>
	<variable cmeta:id="m_A" initial_value="1.0" name="A" units="mV"/>
    
	<variable name="Qmax" public_interface="in" units="per_second"/>
	<variable name="theta" public_interface="in" units="mV"/>
    <variable name="sigma" public_interface="in" units="mV"/>
	<variable name="Qv" public_interface="in" units="per_second"/>
    <variable name="time" public_interface="in" units="hour"/>
	
	<math xmlns="http://www.w3.org/1998/Math/MathML" id="3">
       <apply>
          <eq/>
          <ci>Qm</ci>
          <apply>
             <divide/>
             <ci>Qmax</ci>
             <apply>
                <plus/>
				<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                <apply>
                   <exp/>
				   <apply>
                      <divide/>
					  <apply>
                         <minus/>
						 <apply>
                            <minus/>
                            <ci>Vm</ci>
							<ci>theta</ci>
                         </apply>
					  </apply>
					  <ci>sigma</ci>
				   </apply>
                </apply>
             </apply>
          </apply>
       </apply>
	</math>
	
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="4">	
	   <apply>
          <eq/>
          <apply>
             <diff/>
             <bvar>
                <ci>time</ci>
             </bvar>
             <ci>Vm</ci>
          </apply>
          <apply>
             <divide/>
			 <apply>
                <minus/>
				<apply>
                   <plus/>
				   <ci>A</ci>
				   <apply>
                      <times/>
					  <ci>v_mv</ci>
					  <ci>Qv</ci>
                   </apply>
                </apply>
				<ci>Vm</ci>
             </apply>
			 <apply>
                <divide/>
				<ci>tau_m</ci>
				<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second_per_hour">3600</cn>
			 </apply>
          </apply>
	   </apply>
	</math>
 </component>
 
 <component name="H">
    <variable cmeta:id="H_H" initial_value="15.0" name="H" public_interface="out" units="nM"/>
    
	<variable initial_value="11.0" name="chi" units="hour"/>
	<variable initial_value="3.6" name="mu" units="nM_second"/>
	
	<variable name="Qm" public_interface="in" units="per_second"/>
	<variable name="time" public_interface="in" units="hour"/>
    
	<math xmlns="http://www.w3.org/1998/Math/MathML" id="5">
       <apply>
          <eq/>
          <apply>
             <diff/>
             <bvar>
                <ci>time</ci>
             </bvar>
             <ci>H</ci>
          </apply>
          <apply>
             <divide/>
			 <apply>
                <minus/>
				<apply>
                   <times/>
				   <ci>mu</ci>
				   <ci>Qm</ci>
                </apply>
				<ci>H</ci>
             </apply>
             <ci>chi</ci>
          </apply>
	   </apply>
	</math>
 </component>
 
 <component name="D">
    <variable cmeta:id="D_D" name="D" public_interface="out" units="mV"/>
    
	<variable name="C" units="dimensionless"/>
	<variable initial_value="1.0" name="c0" units="dimensionless"/>
	<variable name="omega" units="per_hour"/>
	<variable initial_value="16.0" name="alpha" units="hour"/>
	<variable initial_value="-3.2" name="v_vc" units="mV"/>
	<variable initial_value="0.19" name="v_vh" units="mV_per_nM"/>
	
	<variable name="H" public_interface="in" units="nM"/>
	<variable name="time" public_interface="in" units="hour"/>
	
	<math xmlns="http://www.w3.org/1998/Math/MathML" id="6">
       <apply>
          <eq/>
          <ci>D</ci>
          <apply>
             <plus/>
			 <apply>
                <times/>
				<ci>v_vc</ci>
				<ci>C</ci>
             </apply>
			 <apply>
                <times/>
				<ci>v_vh</ci>
				<ci>H</ci>
             </apply>
          </apply>
	   </apply>
	</math>
	  
	<math xmlns="http://www.w3.org/1998/Math/MathML" id="7">
       <apply>
          <eq/>
          <ci>C</ci>
          <apply>
             <plus/>
			 <ci>c0</ci>
			 <apply>
                <cos/>
				<apply>
                   <times/>
				   <ci>omega</ci>
				   <apply>
                      <minus/>
					  <ci>time</ci>
					  <ci>alpha</ci>
                   </apply>
                </apply>
		     </apply>
	      </apply>
	   </apply>
	</math>
	
	<math xmlns="http://www.w3.org/1998/Math/MathML" id="8">
       <apply>
          <eq/>
          <ci>omega</ci>
          <apply>
             <divide/>
			 <apply>
                <times/>
				<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
				<pi/>
		     </apply>
			 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="hour">24</cn>
          </apply>
	   </apply>
	</math>
 </component>

 <component name="model_parameters">
    <variable initial_value="100.0" name="Qmax" public_interface="out" units="per_second"/>
	<variable initial_value="10.0" name="theta" public_interface="out" units="mV"/>
    <variable initial_value="3.0" name="sigma" public_interface="out" units="mV"/>
 </component>
 
 
 <connection>
    <map_components component_1="v" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
 </connection>
 
 <connection>
    <map_components component_1="m" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
 </connection>
 
 <connection>
    <map_components component_1="H" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
 </connection>
 
 <connection>
    <map_components component_1="D" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
 </connection>
 
 <connection>
    <map_components component_1="D" component_2="v"/>
    <map_variables variable_1="D" variable_2="D"/>
 </connection>
 
 <connection>
    <map_components component_1="m" component_2="v"/>
    <map_variables variable_1="Qm" variable_2="Qm"/>
	<map_variables variable_1="Qv" variable_2="Qv"/>
 </connection>
 
 <connection>
    <map_components component_1="model_parameters" component_2="v"/>
    <map_variables variable_1="Qmax" variable_2="Qmax"/>
    <map_variables variable_1="theta" variable_2="theta"/>
    <map_variables variable_1="sigma" variable_2="sigma"/>
 </connection>
 
 <connection>
    <map_components component_1="model_parameters" component_2="m"/>
    <map_variables variable_1="Qmax" variable_2="Qmax"/>
    <map_variables variable_1="theta" variable_2="theta"/>
    <map_variables variable_1="sigma" variable_2="sigma"/>
 </connection>
 
 <connection>
    <map_components component_1="m" component_2="H"/>
    <map_variables variable_1="Qm" variable_2="Qm"/> 
 </connection>
 
 <connection>
    <map_components component_1="H" component_2="D"/>
    <map_variables variable_1="H" variable_2="H"/> 
 </connection>

 
 
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"><rdf:Description rdf:nodeID="n1"><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Seq"/></rdf:type><rdf:_2><rdf:Description rdf:nodeID="n2"/></rdf:_2><rdf:_1><rdf:Description rdf:nodeID="n3"/></rdf:_1></rdf:Description><rdf:Description rdf:nodeID="n4"><rdf:type><rdf:Description rdf:about="http://www.example.org/foo/bar/bazfoo"/></rdf:type></rdf:Description><rdf:Description rdf:nodeID="n5"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family></rdf:Description><rdf:Description rdf:nodeID="n6"><subject_type xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">keyword</subject_type><rdf:value><rdf:Description rdf:nodeID="n7"/></rdf:value></rdf:Description><rdf:Description rdf:nodeID="n8"><endingValue xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">400</endingValue></rdf:Description><rdf:Description rdf:nodeID="n3"><Person xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:nodeID="n9"/></Person></rdf:Description><rdf:Description rdf:nodeID="n7"><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Bag"/></rdf:type><rdf:_2 xml:lang="en">neurobiology</rdf:_2><rdf:_1 xml:lang="en">sleep</rdf:_1><rdf:_3 xml:lang="en">diurnal cycle</rdf:_3><rdf:_4 xml:lang="en">circadian rhythms</rdf:_4></rdf:Description><rdf:Description rdf:nodeID="n10"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2009-10-29</W3CDTF></rdf:Description><rdf:Description rdf:nodeID="n11"><Orgname xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Auckland Bioengineering Institute</Orgname></rdf:Description><rdf:Description rdf:nodeID="n12"><rdf:value xml:lang="en">
          This is the CellML description of the Phillips and Robinson 2008 quantitative model of sleep deprivation
        </rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:nodeID="n13"/></creator></rdf:Description><rdf:Description rdf:nodeID="n14"><JournalArticle xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:nodeID="n15"/></JournalArticle><Pubmed_id xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">18805427</Pubmed_id></rdf:Description><rdf:Description rdf:nodeID="n16"><rdf:type><rdf:Description rdf:about="http://imc.org/vCard/3.0#internet"/></rdf:type><rdf:value xml:lang="en">c.lloyd@auckland.ac.nz</rdf:value></rdf:Description><rdf:Description rdf:about=""><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Sleep deprivation in a quantitative physiologically based model of the ascending arousal system (Baseline Model)</title><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:nodeID="n17"/></creator><created xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:nodeID="n10"/></created></rdf:Description><rdf:Description rdf:nodeID="n18"><boundIntervals xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n19"/></boundIntervals></rdf:Description><rdf:Description rdf:nodeID="n9"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:nodeID="n20"/></N></rdf:Description><rdf:Description rdf:nodeID="n21"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">P</Given><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">A</Other><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Robinson</Family></rdf:Description><rdf:Description rdf:nodeID="n22"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2008-12-21</W3CDTF></rdf:Description><rdf:Description rdf:nodeID="n17"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:nodeID="n5"/></N><EMAIL xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:nodeID="n16"/></EMAIL><ORG xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:nodeID="n11"/></ORG></rdf:Description><rdf:Description rdf:nodeID="n23"><subject xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:nodeID="n6"/></subject></rdf:Description><rdf:Description rdf:nodeID="n13"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:nodeID="n20"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">A</Given><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">K</Other><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">J</Other><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Phillips</Family></rdf:Description><rdf:Description rdf:nodeID="n19"><rdf:first><rdf:Description rdf:nodeID="n8"/></rdf:first><rdf:rest><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/></rdf:rest></rdf:Description><rdf:Description rdf:nodeID="n2"><Person xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:nodeID="n24"/></Person></rdf:Description><rdf:Description rdf:about="#phillips_2008"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">
        The Phillips and Robinson 2008 quantitative model of sleep deprivation
      </title><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:nodeID="n23"/></reference><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:nodeID="n14"/></reference><cmeta:comment><rdf:Description rdf:nodeID="n12"/></cmeta:comment><simulation xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n18"/></simulation></rdf:Description><rdf:Description rdf:nodeID="n15"><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:nodeID="n1"/></creator><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">
           Sleep deprivation in a quantitative physiologically based model of the ascending arousal system
          </title><last_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">423</last_page><Journal xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:nodeID="n25"/></Journal><issued xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:nodeID="n22"/></issued><first_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">413</first_page><volume xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">255</volume></rdf:Description><rdf:Description rdf:nodeID="n25"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Journal of Theoretical Biology</title></rdf:Description><rdf:Description rdf:nodeID="n24"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:nodeID="n21"/></N></rdf:Description></rdf:RDF></model>